TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28332	85219;85220;85221	chr2:178561138;178561137;178561136	chr2:179425865;179425864;179425863
N2AB	26691	80296;80297;80298	chr2:178561138;178561137;178561136	chr2:179425865;179425864;179425863
N2A	25764	77515;77516;77517	chr2:178561138;178561137;178561136	chr2:179425865;179425864;179425863
N2B	19267	58024;58025;58026	chr2:178561138;178561137;178561136	chr2:179425865;179425864;179425863
Novex-1	19392	58399;58400;58401	chr2:178561138;178561137;178561136	chr2:179425865;179425864;179425863
Novex-2	19459	58600;58601;58602	chr2:178561138;178561137;178561136	chr2:179425865;179425864;179425863
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-94
• Domain position: 81
• Structural Position: 113
• Q(SASA): 0.5423
• Predicted PPI site: I

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
A/V	None	None	0.944	N	0.449	0.201	0.435043484731	gnomAD-4.0.0	3.60097E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.9375E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
A/C	0.7293	likely_pathogenic	0.732	pathogenic	-0.716	Destabilizing	0.999	D	0.488	neutral	None	None	None	None	I
A/D	0.775	likely_pathogenic	0.7469	pathogenic	-0.743	Destabilizing	0.805	D	0.551	neutral	N	0.501991984	None	None	I
A/E	0.6661	likely_pathogenic	0.6353	pathogenic	-0.903	Destabilizing	0.073	N	0.39	neutral	None	None	None	None	I
A/F	0.6505	likely_pathogenic	0.635	pathogenic	-1.141	Destabilizing	0.996	D	0.653	neutral	None	None	None	None	I
A/G	0.3	likely_benign	0.2861	benign	-0.445	Destabilizing	0.892	D	0.425	neutral	N	0.4623982	None	None	I
A/H	0.8166	likely_pathogenic	0.8096	pathogenic	-0.511	Destabilizing	0.997	D	0.639	neutral	None	None	None	None	I
A/I	0.4759	ambiguous	0.4169	ambiguous	-0.467	Destabilizing	0.987	D	0.525	neutral	None	None	None	None	I
A/K	0.8514	likely_pathogenic	0.8368	pathogenic	-0.579	Destabilizing	0.845	D	0.491	neutral	None	None	None	None	I
A/L	0.367	ambiguous	0.3427	ambiguous	-0.467	Destabilizing	0.916	D	0.492	neutral	None	None	None	None	I
A/M	0.4076	ambiguous	0.3811	ambiguous	-0.261	Destabilizing	0.999	D	0.541	neutral	None	None	None	None	I
A/N	0.6075	likely_pathogenic	0.577	pathogenic	-0.286	Destabilizing	0.975	D	0.636	neutral	None	None	None	None	I
A/P	0.9069	likely_pathogenic	0.8714	pathogenic	-0.411	Destabilizing	0.983	D	0.525	neutral	N	0.478992561	None	None	I
A/Q	0.6693	likely_pathogenic	0.651	pathogenic	-0.639	Destabilizing	0.95	D	0.525	neutral	None	None	None	None	I
A/R	0.7621	likely_pathogenic	0.7491	pathogenic	-0.085	Destabilizing	0.975	D	0.523	neutral	None	None	None	None	I
A/S	0.1348	likely_benign	0.1303	benign	-0.466	Destabilizing	0.243	N	0.258	neutral	N	0.477210969	None	None	I
A/T	0.1859	likely_benign	0.1637	benign	-0.559	Destabilizing	0.805	D	0.461	neutral	N	0.521943181	None	None	I
A/V	0.2533	likely_benign	0.2184	benign	-0.411	Destabilizing	0.944	D	0.449	neutral	N	0.474104263	None	None	I
A/W	0.94	likely_pathogenic	0.933	pathogenic	-1.257	Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	I
A/Y	0.798	likely_pathogenic	0.7897	pathogenic	-0.891	Destabilizing	0.996	D	0.656	neutral	None	None	None	None	I

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.